Urinary proteomic biomarkers to predict cardiovascular events

Proteomics Clin Appl. 2015 Jun;9(5-6):610-7. doi: 10.1002/prca.201400195. Epub 2015 May 15.

Abstract

Purpose: We have previously demonstrated associations between the urinary proteome profile and coronary artery disease (CAD) in cross-sectional studies. Here, we evaluate the potential of a urinary proteomic panel as a predictor of CAD in the hypertensive atherosclerotic cardiovascular disease (HACVD) substudy population of the Anglo-Scandinavian Cardiac Outcomes Trial study.

Experimental design: Thirty-seven cases with primary CAD endpoint were matched for sex and age to controls who had not reached a CAD endpoint during the study. Spot urine samples were analyzed using CE coupled to Micro-TOF MS. A previously developed 238-marker CE-MS model for diagnosis of CAD (CAD238 ) was assessed for its predictive potential.

Results: Sixty urine samples (32 cases; 28 controls; 88% male, mean age 64 ± 5 years) were analyzed. There was a trend toward healthier values in controls for the CAD model classifier (-0.432 ± 0.326 versus -0.587 ± 0.297, p = 0.170), and the CAD model showed statistical significance on Kaplan-Meier survival analysis p = 0.021. We found 190 individual markers out of 1501 urinary peptides that separated cases and controls (AUC >0.6). Of these, 25 peptides were also components of CAD238 .

Conclusion and clinical relevance: A urinary proteome panel originally developed in a cross-sectional study predicts CAD endpoints independent of age and sex in a well-controlled prospective study.

Keywords: Biomarker; Cardiovascular risk; Urinary proteomics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Atherosclerosis / mortality
  • Atherosclerosis / urine
  • Biomarkers / urine
  • Case-Control Studies
  • Coronary Artery Disease / mortality
  • Coronary Artery Disease / urine*
  • Cross-Sectional Studies
  • Female
  • Humans
  • Hypertension / mortality
  • Hypertension / urine
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Peptide Fragments / urine*
  • Prospective Studies
  • Proteome / metabolism
  • Proteomics

Substances

  • Biomarkers
  • Peptide Fragments
  • Proteome